This is a revised renewal application to investigate the biochemistry and biology of human factor VII and tissue factor. The long term goals of the project are to acquire new information concerning factor VII structure-function relationships, the formation and regulation of factor VIIa-tissue factor activity in normal hemostasis, and the control of this activity in pathological coagulation and thrombosis. Specifically, the applicant proposes to: (1) investigate the functional role of O-glycosydically linked carbohydrate in the EGF- domain of factor VIII; (2) to determine the origin of fVIIa in blood; (3) to further elucidate the structural determinants in VII/VIIa required for binding to cell surface tissue factor; (4) to further characterize human TFPI-2 and investigate its role in hemostasis,(5) to study the mechanism of factor VII/VIIa clearance from the blood; and (6) to determine the dynamics of fVII/VIIa binding to cell-surface tissue factor. Aims 4 and 5 are new to this revision, and one specific aim from the original application was deleted because that work is now complete and has been submitted for publication.